• 제목/요약/키워드: SGLT-1

검색결과 17건 처리시간 0.022초

Novel SLC5A2 Mutations and Genetic Characterization in Korean Patients with Familial Renal Glucosuria

  • Lee, Weon Kyung;Oh, Seung Hwan;Chung, Woo Yeong
    • Childhood Kidney Diseases
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    • 제22권2호
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    • pp.37-41
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    • 2018
  • Purpose: Familial renal glucosuria (FRG, OMIM #233100) is a rare but relatively benign genetic condition characterized by persistent isolated glucosuria with a normal blood glucose level. We report three additional SLC5A2 mutations and examine their phenotypic and genetic characteristics in a Korean FRG cohort. We also reviewed the literature and summarized the genotypes of all Korean patients with FRG. Methods: A genetic analysis was conducted by directly sequencing all 14 exons of the SLC5A2 gene and their flanking regions in six unrelated Korean children with FRG and their family members. Novel non-synonymous single-nucleotide polymorphisms were identified and compared with known mutations that are repeatedly detected in the Korean population. Results: We found two novel mutations [c.274G>A (G92S) and c.1168C>T (L390F)] and one known [c.1382G>A (S461N)] mutation in each family and one recurrent mutation [c.1346G>A (G449D) (rs768392222)] in two pedigrees. The recurrent G449D was predicted to be "possibly damaging," with a score of 0.883 in Polyphen-2, while G92S, L390F, and S461N were predicted to be "probably damaging," with scores of 1.000, 0.999, and 0.996, respectively. Conclusions: Two novel, one previously reported, and one recurrent mutation were identified in six Korean FRG pedigrees as causative mutations of renal glucosuria. Sequence variations in the SLC5A2 gene were frequently detected in children with persistent isolated glucosuria. A long-term follow-up of this FRG cohort is needed to understand how these specific SGLT2 mutations impair kidney function and energy homeostasis.

Antidiabetic Activity and Mechanisms of Acarbose in $KKA^{y}$ Mice

  • Kim, Young-Lim;Chung, Sung-Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • 제5권2호
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    • pp.183-188
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    • 2001
  • To elucidate antidiabetic effect and mechanism(s) of acarbose in a polygenic spontaneous hyperglycemic and hyperinsulinemic diabetic animal model, $KKA^y$ mice, acarbose was administered orally for 4 weeks and effects on body weight, plasma glucose and insulin levels, genetic expressions of intestinal sucrase-isomaltase (SI), sodium-glucose cotransporter (sGLT1) and glucose transporter in quadriceps muscle (GLUT4) were examined in this study. Although no differences in body weight were detected between control and acarbose-treated groups, plasma glucose level in acarbose-treated group was markedly reduced as compared to the control. In the mechanism study, acarbose downregulated the SI and SGLT1 gene expressions, and upregulated the GLUT4 mRNA and protein expressions when compared to the control group. In conclusion, the data obtained strongly implicate that acarbose can prevent the hyperglycemia in $KKA^y$ mice possibly through blocking intestinal glucose absorption by downregulations of SI and sGLT1 mRNA expressions, and upregulation of skeletal muscle GLUT4 mRNA and protein expressions.

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Effect of Corticosterone Administration on Small Intestinal Weight and Expression of Small Intestinal Nutrient Transporter mRNA of Broiler Chickens

  • Hu, X.F.;Guo, Yuming;Huang, B.Y.;Zhang, L.B.;Bun, S.;Liu, D.;Long, F.Y.;Li, J.H.;Yang, X.;Jiao, P.
    • Asian-Australasian Journal of Animal Sciences
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    • 제23권2호
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    • pp.175-181
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    • 2010
  • The effects of corticosterone (CORT) administration on the weight of small intestine and the expression of nutrient transporter mRNA in the small intestine of broiler chickens (Gallus gallus domesticus) were investigated. One hundred and eight sevenday-old birds were randomly divided into two equal groups comprising a control group (CTRL) and an experimental group (CORT). CTRL birds were fed a basal diet and the CORT birds were fed a basal diet containing 30 mg corticosterone/kg from d 8 to 21. At 21 d of age, average daily feed intake (ADFI), serum corticosterone level, small intestinal absolute wet weight and relative weight, and relative abundance of SGLT1, CaBP-D28k, PepT1 mRNA in the duodenum and L-FABP mRNA in the jejunum were determined. The results showed that serum corticosterone level, liver weight and small intestinal relative weight (small intestinal wet weight/body weight) of CORT chickens were about 30.15%, 26.72% and 42.20% higher, respectively, than in the CTRL group (p<0.05). CORT birds had relative mRNA abundance of CaBP-D28k and PepT1 in the duodenum, and L-FABP in the jejunum which was 1.77, 1.37 and 1.94 fold higher, respectively, than in the CTRL group (p<0.05); the relative abundance of SGLT1 was 1.67 fold higher than in the CTRL group (p = 0.097). ADFI, small intestinal wet weight and length in CORT-treated broiler chickens was about 29.11%, 31.12% and 12.35% lower, respectively, than in the CTRL group (p<0.05). In conclusion, corticosterone administration lowered the wet weight but increased the relative weight of the small intestine and the expression of intestinal nutrient transporter mRNA of broiler chickens.

The effect of multi-strain probiotics as feed additives on performance, immunity, expression of nutrient transporter genes and gut morphometry in broiler chickens

  • Biswas, Avishek;Dev, Kapil;Tyagi, Pramod K;Mandal, Asitbaran
    • Animal Bioscience
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    • 제35권1호
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    • pp.64-74
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    • 2022
  • Objective: This study was conducted to investigate the effects of dietary multi-strain probiotic (MSP) (Bacillus coagulans Unique IS2 + Bacillus subtillis UBBS14 + Saccharomyces boulardii Unique 28) on performance, gut morphology and expression of nutrient transporter related genes in broiler chickens. Methods: A total of 256 (4×8×8) day-old CARIBRO Vishal commercial broiler chicks of uniform body weight were randomly distributed into four treatments with 8 replicates each and having eight chicks in each replicate. Four dietary treatments were T1 (negative control-basal diet), T2 (positive control-antibiotic bacitracin methylene disalicylate at 20 mg/kg diet), T3 (MSP at 107 colony-forming unit [CFU]/g feed), and T4 (MSP at 108 CFU/g feed). Results: During 3 to 6 weeks and 0 to 6 weeks, the body weight gain increased significantly (p<0.05) in T3 and T4 groups. The feed intake significantly (p<0.05) reduced from T1 to T3 during 0 to 3 weeks and the feed conversion ratio also significantly (p<0.05) improved in T3 and T4 during 0 to 6 weeks. The humoral and cell mediated immune response and the weight of immune organs were also significantly (p<0.05) improved in T3 and T4. However, significant (p<0.05) dietary effects were observed on intestinal histo-morphometry of ileum in T3 followed by T4 and T2. At 14 d post hatch, the relative gene expression of glucose transporter (GLUT5), sodium-dependent glucose transporter (SGLT1) and peptide transporter (PepT1) showed a significant (p<0.05) up-regulating pattern in T2, T3, and T4. Whereas, at 21 d post hatch, the gene expression of SGLT1 and PepT1 was significantly (p<0.05) downregulated in MSP supplemented treatments T3 and T4. Conclusion: The supplementation of MSP at 107 CFU/g diet showed significant effects with improved performance, immune response, gut morphology and expression of nutrient transporter genes. Thus, the MSP could be a suitable alternative to antibiotic growth promoters in chicken diets.

제2형 당뇨병 환자에서 Dapagliflozin이 혈당과 심혈관계질환 위험인자에 미치는 영향 및 안전성 (Dapagliflozin's Effects on Glycemia and Cardiovascular Risk Factors and Incidence of Adverse Events in Patients with Type 2 Diabetes)

  • 이혜진;금민정;김재송;김수현;손은선
    • 한국임상약학회지
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    • 제27권4호
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    • pp.214-220
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    • 2017
  • Background: Dapagliflozin is an oral selective inhibitor of sodium-glucose cotransporter 2(SGLT2), the kidney transporter chiefly responsible for glucose reabsorption from the glomerular filtrate. Because this mechanism does not require the action of insulin, dapagliflozin rarely causes hypoglycemia. Dapagliflozin may affect blood glucose control as well as blood pressure and the body weight which are one of the cardiovascular disease risk factors. However, dehydration and ketoacidosis are reported as the side effects of the dapagliflozin treatment and the safety issues have been occurred. The aim of this study is to analyze the effectiveness and adverse events of dapagliflozin in Korean patients. Methods: From December 2014 to August 2015, we retrospectively reviewed the electronic medical records of type 2 diabetes patients who were prescribed dapagliflozin at Severance Hospital. Results: A total of 202 Korean patients were enrolled in this study. The effectiveness in the reduction of blood glucose was statistically significant(p<0.001). Dapagliflozin decreased 0.74% of HbA1c after 24 weeks. Significantly more participants achieved the target HbA1c level(HbA1c<7%) after 24 weeks(n=42, 35.3%) than before taking dapagliflozin(n=21, 17.6%). Blood pressure decreased 5.7 mmHg systolic blood pressure(SBP), 1.9 mmHg diastolic blood pressure(DBP) after 24 weeks. More than one quarter of participants(n=35, 29.4%) experienced weight loss. Most common adverse event was genitourinary symptoms. Conclusion: In this study, the effectiveness of dapagliflozin in improving glycemic control, blood pressure control, and weight loss was statistically significant. However, elderly and female patients, who have higher incidence of adverse events, should use dapagliflozin cautiously.

Effects of Immune Stress on Performance Parameters, Intestinal Enzyme Activity and mRNA Expression of Intestinal Transporters in Broiler Chickens

  • Feng, Y.;Yang, X.J.;Wang, Y.B.;Li, W.L.;Liu, Y.;Yin, R.Q.;Yao, J.H.
    • Asian-Australasian Journal of Animal Sciences
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    • 제25권5호
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    • pp.701-707
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    • 2012
  • Immune stress is the loss of immune homeostasis caused by external forces. The purpose of this experiment was to investigate the effects of immune stress on the growth performance, small intestinal enzymes and peristalsis rate, and mRNA expression of nutrient transporters in broiler chickens. Four hundred and thirty-two 1-d-old broilers (Cobb500) were randomly assigned to four groups for treatment; each group included nine cages with 12 birds per cage. Group 1 = no vaccine (NV); Group 2 = conventional vaccine (CV); group 3 = lipopolysaccharide (LPS)+conventional vaccine (LPS); group 4 = cyclophosphamide (CYP)+conventional vaccine (CYP). The results demonstrated that immune stress by LPS and CYP reduced body weight gain (BWG), feed intake (FI), small intestine peristalsis rate and sIgA content in small intestinal digesta (p<0.05). However, the feed conversion ratio (FCR) remained unchanged during the feeding period. LPS and CYP increased intestinal enzyme activity, relative expression of SGLT-1, CaBP-D28k and L-FABP mRNAs (p<0.05). LPS and CYP injection had a negative effect on the growth performance of healthy broiler chickens. The present study demonstrated that NV and CV could improve growth performance while enzyme activity in small intestine and relative expression of nutrient transporter mRNA of NV and CV were decreased in the conditions of a controlled rational feeding environment. It is generally recommended that broilers only need to be vaccinated for the diseases to which they might be exposed.

Dietary effects of sophorolipids on nutrient bioavailability and intestinal microenvironments in broiler chickens

  • Min-Jin, Kwak;Min Young, Park;Ki-Peum, Sung;Hanbae, Lee;Kwang-Youn, Whang;Younghoon, Kim
    • Journal of Animal Science and Technology
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    • 제64권6호
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    • pp.1092-1104
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    • 2022
  • Using antibiotics as growth promoter has been banned in poultry feed industry, thus various researchers try to seek an alternative to replace the growth-promoting antibiotics. In this study, we aimed to evaluate the growth performance via intestinal nutrient utilization and cecal microbial composition of broiler after dietary supplementation with most commonly using antibiotics, zinc bacitracin, and sophorolipid. A total of 180 1-day-old chicks were randomly assigned, and dietary treatment was as follow: CON, basal diet; ZB, 100 ppm of zinc bacitracin supplemented diet; and SPL, 250 ppm of sophorolipid supplemented diet. Their growth performance was evaluated and the samples of blood, small intestine, and ileal and cecal digesta were collected for biochemical, histological, and genomic analyses. The body weight and average daily gain of 7-day-old chicks were higher in ZB and those in overall experimental period were improved by ZB and SPL supplementation (p < 0.05). Their intestinal characteristics were not affected by dietary treatments in duodenum and ileum. Nonetheless, villus height was increased by SPL supplementation in jejunum (p < 0.05). Moreover, dietary SPL supplementation could down-regulate the expression level of pro-inflammatory cytokine, IL-1β (p < 0.05). mRNA levels of lipid and protein transporters did not differ among the treatments, however, relative expression levels of carbohydrate transporters, GLUT2 and SGLT1 were increased in broiler chicken's jejumum fed zinc bacitracin and sophorolipid supplemented diets (p < 0.05). Dietary zinc bacitracin supplementation could increase the population of Firmicutes in phylum level, and the portion of Turiciacter in genus level. On the other hands, the portion of Faecalibacterium was increased by dietary SPL supplementation compared to the other treatments. Our findings suggest that SPL supplementation improves growth performance through enhanced carbohydrate utilization capacity via improvement of gut morphological status and modulation of the cecal microbial population of broilers.